TY - JOUR A1 - Nagata, Takashi A1 - Suzuki, Sakura A1 - Endo, Ryuta A1 - Shirouzu, Mikako A1 - Terada, Takaho A1 - Inoue, Makoto A1 - Kigawa, Takanori A1 - Kobayashi, Naohiro A1 - Güntert, Peter A1 - Tanaka, Akiko A1 - Hayashizaki, Yoshihide A1 - Muto, Yutaka A1 - Yokoyama, Shigeyuki T1 - The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition T2 - Nucleic acids research N2 - The degradation of the poly(A) tail is crucial for posttranscriptional gene regulation and for quality control of mRNA. Poly(A)-specific ribonuclease (PARN) is one of the major mammalian 3’ specific exo-ribonucleases involved in the degradation of the mRNA poly(A) tail, and it is also involved in the regulation of translation in early embryonic development. The interaction between PARN and the m7GpppG cap of mRNA plays a key role in stimulating the rate of deadenylation. Here we report the solution structures of the cap-binding domain of mouse PARN with and without the m7GpppG cap analog. The structure of the cap-binding domain adopts the RNA recognition motif (RRM) with a characteristic a-helical extension at its C-terminus, which covers the b-sheet surface (hereafter referred to as PARN RRM). In the complex structure of PARN RRM with the cap analog, the base of the N7-methyl guanosine (m7G) of the cap analog stacks with the solvent-exposed aromatic side chain of the distinctive tryptophan residue 468, located at the C-terminal end of the second b-strand. These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains. KW - binding sites KW - gene expression regulation KW - guanosine KW - helix (snails) KW - mammals KW - multiple sclerosis KW - relapsing-remitting KW - nucleotides KW - quality control KW - rna KW - messenger KW - solvents KW - tryptophan KW - mice KW - ribonucleases KW - embryologic development KW - titration method KW - catabolism KW - rna recognition motif Y1 - 2008 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/5840 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-57809 SN - 0305-1048 SN - 1362-4962 N1 - © 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. VL - 36 IS - 14 SP - 4754 EP - 4767 PB - Oxford Univ. Press CY - Oxford ER -